Liu Ningning, Tan Jiang-Shan, Liu Lu, Wang Yufeng, Hua Lu, Qian Qiujin
Peking University Sixth Hospital/Institute of Mental Health, Beijing, China.
NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China.
Front Psychiatry. 2021 Oct 20;12:746276. doi: 10.3389/fpsyt.2021.746276. eCollection 2021.
The outbreak of 2019 coronavirus disease (COVID-19) has become a global pandemic. Although it has long been suspected that COVID-19 could contribute to the development of mental illness, and individuals with a pre-existing mental illness may have a higher risk of and poorer outcomes from COVID-19 infection, no evidence has established a causal association between them thus far. To investigate associations in support of a causal association between the severity of COVID-19 and mental illnesses, we leveraged large-scale genetic summary data from genome-wide association study (GWAS) summary datasets, including attention-deficit/hyperactivity disorder (ADHD) ( = 55,374), schizophrenia ( = 77,096), bipolar disorder ( = 51,710), and depression ( = 173,005), based on a previous observational study. The random-effects inverse-variance weighted method was conducted for the main analyses, with a complementary analysis of the weighted median and MR-Egger approaches and multiple sensitivity analyses assessing horizontal pleiotropy and removing outliers in two different COVID-19 databases. The Mendelian randomization (MR) analysis indicated that ADHD [odds ratio (OR) = 1.297; 95% confidence interval (CI), 1.029-1.634; = 0.028] increased the risk of hospitalization due to COVID-19. A similar association was obtained in MR sensitivity analyses of the weighted median. In addition, genetically predicted COVID-19 was significantly associated with schizophrenia (OR = 1.043; 95% CI, 1.005-1.082; = 0.027). Although many studies have reported a causal relationship between COVID-19 and mental illness, our study shows that this increased risk is modest. However, considering the characteristics of ADHD that might further increase the individuals' vulnerability to being infected by COVID-19, the ongoing massive worldwide exposure to COVID-19, and the high burden of schizophrenia, we believe that it is necessary to offer preventative measures to these populations and to provide more evidence in understanding the neurological impact of COVID-19.
2019冠状病毒病（COVID-19）的爆发已成为全球大流行。尽管长期以来人们一直怀疑COVID-19可能导致精神疾病的发生，而且患有既往精神疾病的个体感染COVID-19的风险可能更高、预后更差，但迄今为止尚无证据证实它们之间存在因果关联。为了研究支持COVID-19严重程度与精神疾病之间因果关联的相关性，我们基于之前的一项观察性研究，利用了全基因组关联研究（GWAS）汇总数据集的大规模遗传汇总数据，包括注意力缺陷多动障碍（ADHD）（n = 55,374）、精神分裂症（n = 77,096）、双相情感障碍（n = 51,710）和抑郁症（n = 173,005）。主要分析采用随机效应逆方差加权法，并对加权中位数和MR-Egger方法进行补充分析，以及在两个不同的COVID-19数据库中进行多重敏感性分析，评估水平多效性并去除异常值。孟德尔随机化（MR）分析表明，ADHD [优势比（OR）= 1.297；95%置信区间（CI），1.029 - 1.634；P = 0.028]会增加因COVID-19住院的风险。在加权中位数的MR敏感性分析中也获得了类似的关联。此外，基因预测的COVID-19与精神分裂症显著相关（OR = 1.043；95% CI，1.005 - 1.082；P = 0.027）。尽管许多研究报告了COVID-19与精神疾病之间的因果关系，但我们的研究表明这种增加的风险是适度的。然而，考虑到ADHD的特征可能会进一步增加个体感染COVID- 的易感性、全球范围内持续大量暴露于COVID-19以及精神分裂症的高负担，我们认为有必要为这些人群提供预防措施，并在理解COVID-19对神经系统的影响方面提供更多证据。
